PROJECT SUMMARY The Cell Biology/Morphology Core provides BADERC investigators with technical support, equipment, advice and expertise for cell biological, immunocytochemical and morphological studies related to cell/membrane biology and signal transduction; cellular immunology and islet cell biology; and vascular and endothelial cell biology. The Core occupies space in the MGH Program in Membrane Biology facility on the 8th floor of the Simches Research Center, which is adjacent to the MGH main campus. The Core Director, Dr. Brown, has considerable expertize in the area of membrane biology, membrane proteins, and intracellular trafficking. He and his colleagues have a long and well-established track record of operating similar Core facilities in the context of other Centers and Program Projects over the past 25 years, including previous iterations of this BADERC Core. The aim of the Core is to provide an integrated cellular imaging solution to problems in Diabetes and other targeted research areas at a time when few or no isolated laboratories can develop the highest level of technical competence in the important and specialized areas served by the Core. The Cell Biology Core is designed to maximize the use and availability of several specialized items of equipment, that are not only prohibitively expensive for many laboratories, but that also require expensive and regular maintenance. This includes all aspects of microscopy from routine immunofluorescence work, confocal imaging, and (immuno)electron microscopy. The Core is especially proud of its record in successfully attracting NIH Shared Instrumentation Grants (SIGs) and institutional support over the years. With support of Core users, we have obtained 5 SIGs in little more than 10 years, the most recent of which was a $700K award in 2012 for a new Nikon A1R confocal platform that can offer sophisticated imaging and analysis capabilities to BADERC users including fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP). In addition, a total internal reflection fluorescence microscope (TIRF) was purchased with MGH institutional funding, along with other important Core equipment over the years. Thus, the Core is continually striving to evolve and upgrade its equipment and expertize to allow its users to perform cutting edge research, and the MGH clearly appreciates the value of its services. A major and important objective of the Core is to provide an environment for the training of key personnel from participating laboratories, a strategy that has worked very successfully over the prior funding periods. Dr. Brown and his highly-qualified technical support staff have well-established and proven procedures in place for maximizing Core use in the context of varied projects and specific experimental requirements. The bottom line is that this Core works smoothly and well, and has done so for over two decades. Its use has resulted in several hundred publications over that time that contain images taken by Core staff, or by trained users, including over 60 in the previous BADERC funding period. We expect this to continue based on the usage proposed in this application.